title: Strong prediction of virological response to combination therapy by IL28B gene variants rs12979860 and rs8099917 in chronic hepatitis C genotype 4.
abstract: BACKGROUND
  A strong association between single nucleotide polymorphisms (SNPs) of IL28B and treatment outcomes of pegylated interferon-α (PEG IFNα) and ribavirin (RBV) has been shown in chronic hepatitis C (CHC) patients with genotype 1.
  
  
  OBJECTIVE
  This study aimed to assess two SNPs of IL28B, rs12979860 and rs8099917, in predicting sustained virological responses (SVR) to treatment of CHC patients with genotype 4 (HCV-4). The value of rs8099917 was investigated in carriers of unfavourable genotypes of rs12979860.
  
  
  METHODS
  This study included 119 CHC patients with HCV-4 receiving combination therapy. Both SNPs of IL28B were determined by real-time detection polymerase chain reaction.
  
  
  RESULTS
  Genotypes CC/CT/TT of rs12979860 were found in 42 (35.3%), 56 (47.1%) and 21 (17.6%) and rs8099917 TT/TG/GG were found in 74 (62.2%), 40 (33.6%) and 5 (4.2%). In carriers of rs12979860 CC and rs8099917 TT, the rate of SVR was 87.5 and 65.7% respectively. In 54 patients heterozygous for the C allele of rs12979860, testing of rs8099917 revealed SVR in 42.3% of carriers of the TT genotype but no such responses in carriers of TG or GG (P < 0.0001, OR = 47.3, 95% CI: 2.33-767.2). By multivariate analysis, predictors of SVR were baseline ALT (P = 0.014, OR = 6.3, 95% CI: 1.45-27.33), rs12979860 CC (P = 0.001, OR = 13.48, 95% CI: 2.95-61.69) and rs8099917 TT (P = 0.027, OR = 7.5, 95% CI: 1.25-44.88).
  
  
  CONCLUSIONS
  In CHC genotype 4 patients, favourable genotypes of both SNPs of IL28B are valuable for predicting SVR. Additional genotyping of rs8099917 in carriers of the heterozygous C allele of rs12979860 can improve the prediction of SVR.
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
authors.forename: Mostafa M
authors.initials: MM
authors.lastname: Ragheb
authors.forename: Nader A
authors.initials: NA
authors.lastname: Nemr
authors.forename: Rania M
authors.initials: RM
authors.lastname: Kishk
authors.forename: Mohamed F
authors.initials: MF
authors.lastname: Mandour
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Abdou
authors.forename: Kentaro
authors.initials: K
authors.lastname: Matsuura
authors.forename: Tsunamasa
authors.initials: T
authors.lastname: Watanabe
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D004359:Drug Therapy, Combination; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D006579:Heterozygote; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D018579:Patient Selection; D010597:Pharmacogenetics; D010641:Phenotype; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a
keywords: HCV; IL28B; SVR; genotype 4; rs12979860; rs8099917